What side effects are associated with this type of intervention?

Common treatments for Semantic Dementia, such as cholinesterase inhibitors (e.g., donepezil) and NMDA receptor antagonists (e.g., memantine), often have side effects including gastrointestinal issues (nausea, diarrhea), headaches, dizziness, and potential cardiovascular effects. For myeloperoxidase inhibitors like Verdiperstat, while specific side effects are not well-documented, similar agents may cause gastrointestinal discomfort, liver enzyme abnormalities, and potential hematologic effects. It is important to monitor patients closely for any adverse reactions during treatment.

What prior FDA approvals exist?

There are no specific FDA-approved treatments for Semantic Dementia mentioned in the provided context. Verdiperstat, a myeloperoxidase inhibitor, is currently being studied for its potential benefits in treating semantic variant primary progressive aphasia (svPPA) due to TDP-43 pathology. Broader treatments for related neurodegenerative conditions, such as Alzheimer's disease, include drugs like aducanumab, which targets amyloid plaques, and antioxidants like vitamin E. However, these treatments are not specifically approved for Semantic Dementia.

What other types of research exist?

Promising novel alternatives to Verdiperstat for Semantic Dementia (svPPA) patients include gosuranemab, an anti-tau monoclonal antibody, and SM07883, a potent, selective oral DYRK1A inhibitor. Both target mechanisms relevant to neurodegenerative diseases and have shown potential in clinical trials.

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Verdiperstat for Frontotemporal Dementia (Veri-T-001 Trial)

Phase 1

Recruiting

Research Sponsored by Peter Ljubenkov, MD

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Able to swallow pills whole without crushing or chewing

MRI at screening is consistent with the underlying svPPA with no large strokes or severe white matter disease (Fazekas Grade ≤2; Fazekas et al. 1987)

Must not have

Pathologic renal findings at screening as defined by the presence of either of the following criteria: Estimated glomerular filtration rate (eGFR) [determined by the Modification of Diet in Renal Disease (MDRD) Study equation] < 30 milliliter (mL)/minute/1.73 square meter (m2). The MDRD Study equation is as follows: eGFR (mL/minute/1.73 m2) = 175 x (Scr)-1.154 x (Age)-0.203 x (0.742 if female) x (1.212 if African American), where Scr = serum creatinine in mg/deciliter (dL) as measured by a method calibrated to an isotope dilution mass spectrometry (IDMS) reference method; Serum creatinine ≥ 2.5 mg/dL; Hemoglobin A1C >7.5% at screening (confirmed by repeat)

A clinical diagnosis of probable AD (McKhann et al. 2011) or previous biomarker evidence of AD biology using amyloid positron emission tomography (PET) imaging, CSF amyloid beta (Aβ)/total tau (t-tau) ratio, CSF/plasma amyloid beta isoform with 40 amino acid residues (Aβ40)/amyloid beta isoform with 42 amino acid residues (Aβ42) ratio, or plasma phosphorylated tau [phosphorylated tau at residue 181 (p-tau181) and phosphorylated tau at residue 217 (p-tau217)] assessments

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 24 weeks

Summary

This trial tests the safety of Verdiperstat, a medication taken regularly, in patients with language difficulties caused by brain issues. The study aims to see if the drug can change protein levels in the brain and improve cognitive functions.

Who is the study for?

This trial is for adults aged 18-85 with semantic variant primary progressive aphasia due to TDP-43 pathology. Participants must be able to swallow pills, have a study partner, and agree to contraception if of childbearing potential. Exclusions include significant cardiovascular, renal or hepatic disease; recent immunosuppressants use; certain blood disorders; uncontrolled thyroid disease; major psychiatric illness; and known sensitivity to Verdiperstat's ingredients.

What is being tested?

The Veri-T trial is testing the safety and effectiveness of Verdiperstat taken twice daily by patients with svPPA due to FTLD-TDP. The study will last for 24 weeks where three-fourths of participants receive Verdiperstat and one-fourth receive a placebo.

What are the potential side effects?

While specific side effects are not listed here, common concerns in trials like this may include digestive issues, potential allergic reactions, changes in mood or behavior, fatigue, headaches or other neurological symptoms.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I can swallow pills whole without needing to crush or chew them.

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My MRI shows svPPA without major strokes or severe brain damage.

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I am between 18 and 85 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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Your kidney function, as measured by eGFR, is very low, and your serum creatinine or Hemoglobin A1C levels are too high.

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I have been diagnosed with Alzheimer's disease based on specific tests.

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I have no GI diseases or surgeries that affect drug absorption.

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I haven't had a heart attack or been hospitalized for heart issues in the last year.

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My thyroid disease is not under control, with abnormal T4 and very high TSH levels.

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I have previously been treated with verdiperstat.

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I do not have a history of serious heart, blood, kidney, or liver diseases.

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I haven't taken strong CYP1A2 inhibitors like ciprofloxacin recently.

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My cancer was diagnosed within the last 5 years, excluding skin cancer.

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I haven't taken steroids or immune-weakening drugs in the last 30 days.

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I have a serious autoimmune disease or a condition that weakens my immune system.

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I do not have any medical conditions like uncontrolled seizures or substance abuse that could explain my cognitive or behavioral issues.

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I have undergone stem cell treatment.

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I do not have a significant viral infection, including HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 24 weeks

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~24 weeks

This trial's timeline: 3 weeks for screening, Varies for treatment, and 24 weeks for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of Treatment-Emergent Adverse Events

Secondary study objectives

Changes in Pharmacokinetic properties of Verdiperstat in Cerebrospinal Fluid (CSF)

Changes in Pharmacokinetic properties of Verdiperstat in Plasma

Other study objectives

Change in Clinical Dementia Rating Scale (CDR-SB)

Change in Executive brain function

Change in brain volume on brain MRI

+7 more

Side effects data

From 2022 Phase 2 & 3 trial • 167 Patients • NCT04436510

28%

Nausea

21%

Headache

20%

Insomnia

19%

Fall

19%

Constipation

17%

Muscular weakness

16%

Fatigue

13%

Neuromyopathy

10%

Tension headache

10%

Dizziness

10%

Decreased appetite

10%

Dysphagia

Blood thyroid stimulating hormone increased

Dyspnoea

Diarrhoea

Urinary tract infection

Salivary hypersecretion

Anxiety

Urine odour abnormal

Cough

Back pain

Arthralgia

Oedema peripheral

Pain in extremity

Dysarthria

Pulmonary embolism

Respiratory failure

Amyotrophic lateral sclerosis

Febrile neutropenia

Bacteraemia

Abdominal pain

Cerebral infarction

Deep vein thrombosis

B-cell lymphoma

Acute respiratory failure

COVID-19

COVID-19 pneumonia

Dehydration

Sudden death

Aphasia

Bacterial sepsis

Failure to thrive

Hip fracture

Ileus

Hepatic enzyme abnormal

100%

80%

60%

40%

20%

Study treatment Arm

Verdiperstat

Matching Placebo

Trial Design

2Treatment groups

Experimental Treatment

Placebo Group

Group I: VerdiperstatExperimental Treatment1 Intervention

Verdiperstat 2 tablets twice daily (600mg total daily) by mouth for 24 weeks.

Group II: PlaceboPlacebo Group1 Intervention

Placebo 2 tablets twice daily by mouth for 24 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Verdiperstat

2019

Completed Phase 3

~610

0 / 17Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Verdiperstat, a Myeloperoxidase Inhibitor, is being studied for its potential to treat Semantic Dementia by targeting neuroinflammation. Myeloperoxidase is an enzyme involved in the production of reactive oxygen species, which can contribute to oxidative stress and inflammation in the brain. By inhibiting this enzyme, Verdiperstat aims to reduce neuroinflammation and oxidative damage, which are believed to play a role in the progression of neurodegenerative diseases like Semantic Dementia. This mechanism is crucial for patients as it addresses underlying pathological processes, potentially slowing disease progression and improving cognitive function.

Memantine for dementia.Effect of galantamine on verbal repetition in AD: a secondary analysis of the VISTA trial.Utilizing combination therapy in the treatment of Alzheimer's disease.